Cytoplasmic factors present in mature metaphase II arrested (MII) oocytes have a unique activity to reset the identity of transplanted somatic cell nuclei to the embryonic state. Since the initial discovery in amphibians (Gurdon J B, J Embryology, Exp Morphology 10, 622-640 (1962); incorporated by reference herein), SCNT success in a range of different mammalian species demonstrated that this reprogramming activity in enucleated oocytes (cytoplasts) is universal (Solter D, Nat Rev Genet 1, 199-207 (2000) and Wilmut I et al, Nature 419, 583-586 (2002); both of which are incorporated by reference herein). However, despite numerous applications of SCNT for animal cloning, the nature of reprogramming oocyte factors and the mechanism of their action remain largely unknown.
Pluripotent stem cells have been produced by somatic cell nuclear transfer in non-human primates (U.S. Pat. No. 7,972,849; incorporated by reference herein.) In humans, SCNT has been envisioned as a method of generating personalized embryonic stem cells from a patient's somatic cells that could be used to study the mechanisms of disease and ultimately to be used for cell based therapies (Lanza R P et al, Nature Biotech 17, 1171-1174 (1999) and Yang X et al, Nature Genet 39, 295-302 (2007); both of which are incorporated by reference herein). However, derivation of human nuclear transfer derived ESCs (NT-ESCs) has not been achieved, despite numerous attempts over the past decade.